XMRV vs HIV and long-term anti-retrovirals

I have a question. I'm sure we're all anxious about the long-term effects of having a retrovirus and about the toxic long-term effects of anti-retrovirals. Like everyone I've been trying to roll with the punches on the XMRV story and one aspect that keeps me cheerful is that, unlike people who are HIV+ who always (I believe) get sicker and sicker if untreated, many people with ME/CFS either stay stable or improve over time.

So, my question: if XMRV turns out to be "it", is it likely that we could be put on a short (compared to HIV) course of anti-retrovirals that would be sufficient to reduce our viral load to the point where our bodies natural defences could pretty much keep a lid on it? Maybe with a top-up now and again?

I got sick with ME after a viral infection over 20 years ago, with classic ME symptoms (post-exertional malaise, the usual) and was so ill that I was confined to bed for 7 years. Then I gradually got better (with no treatment) and was able to work again, although with minor relapses. Now I am in a big relapse and have been pretty much housebound for the last few years. So I know firsthand that even those of us with severe ME/CFS can make a big recovery if our bodies get a chance to fight back; and that even so, it doesn't go away and our bodies can be overwhelmed again. If XMRV is behind ME/CFS, presumably this is to do with viral load; and if our bodies can keep it low for long periods, would we need antiretrovirals in the long term?

Sorry if this is either (a) in the wrong place or (b) nuts. I'm curious to know what our bioscience brains think here on the forum!

I have wondered about this, too. If XMRV is the culprit, two things seem to offer some hope for a limited treatment period, followed by a drug-free remission: 1) some people with CFS get better and 2) about 9 out of 10 people that are XMRV positive are not sick according to Lombardi et al. Of course both of these could be due to extra genetic susceptibility on the part of those who are really sick, and achieving escape velocity may not be possible for such people.

The problem I see with ART (anti retroviral therapy) for XMRV is that per Mikovitz XMRV is very, very slow replicating. It only replicates when the cell divides. This puts the virus in a completely different category from HIV, which is rapidly mutating and always active. So while ART helps people with AIDS, often dramatically, the effect of ART for XMRV might be much less significant. Basically, if you stop a slow replication process you will only have a reduction of infection when old cells divide. But the damage done to the currently infected cells will persist as long as that cell is alive. ART can not change that. So whatever XMRV does to our DNA (it replaces some small section), whatever rogue proteins are being produced, or whatever good protein production is being blocked, that will continue even while ART is used. That damage will only stop when all of the old infected cells in the body have been replaced, which might take years.

What seems more probable, if XMRV is really involved in creating CFS and not just a passenger virus, is that treatment will have to include a combination of low-level ART to reduce viral activity during cell replication, along with treatments to mitigate the problems the XMRV has caused in cellular DNA in the various reservoirs throughout the body. That might be a very complicated problem to solve.

So if people try ART for CFS and they are dramatically helped rapidly, that will make me suspect that some other retrovirus is involved in CFS and not just XMRV, and that ART is controlling some other unknown retroviral problem.

This situation is REALLY unpredictable at the moment. We have yet to see a single credible validation study for the WPI finding, and there is not yet a good causal model, nor proof that XMRV is anything other than a passenger virus. There is a very long road ahead for XMRV.

One other note, people with AIDS who tolerate ART well rapidly become healthier than most CFS patients. In other words, as their health improves they probably better tolerate the toxic nature of ART. With CFS I suspect researchers will find out that some other treatment is required, and that ART is far too toxic for the highly drug-sensitive CFS patients, particularly given the probable long duration of therapy and the very gradual improvement that will result.

This is a good question. While we still don't know that XMRV causes CFS, I believe it's interesting to look at what happens to people who undergo chemotherapy for cancer. Chemotherapy treatment for me greatly decreased my weakness/fatigue. I enjoyed the irony of the situation...people were bringing me meals, running errands for me, and in some respects, I hadn't felt that good in years!

Keep in mind that steroids are often given with chemo treatments, and as Rich VanK has pointed out, bioavailable forms of folic acid are also given.

Having said all that, my belief is that occasional treatment may just do the trick.

...one aspect that keeps me cheerful is that, unlike people who are HIV+ who always (I believe) get sicker and sicker if untreated, many people with ME/CFS either stay stable or improve over time.

So, my question: if XMRV turns out to be "it", is it likely that we could be put on a short (compared to HIV) course of anti-retrovirals that would be sufficient to reduce our viral load to the point where our bodies natural defences could pretty much keep a lid on it? Maybe with a top-up now and again?

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I have been extremely stable over the past 10 years...my condition is more consistent month to month and year to year (more so than from one day to another).

I am hoping that this is the case. Apparently most people with XMRV are not sick, so perhaps if we are able to get our viral loads down and fix our immune system and recover from this illness, we can stay that way without drugs. I like to think that what happens is we get "stuck" in CFS because it is so stable, but if we can fix that we can also get "stuck" in a healthy mode that is also stable.

Where do you read that? Which cells divide? You mean it replicates with the lysogenic cycle? I thought that was only applicable to bacteria, as human cells don't clone each other--at least NK, B, and T cells, don't "divide". They come from stem cells in the bone marrow.

That damage will only stop when all of the old infected cells in the body have been replaced, which might take years.

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Not necessarily, as immune modulators would speed up the process, I don't see why it would take years. Two of Cheney's stem cell patients had full recoveries after 6-7 months, after being sick for 15 years or so.

Where do you read that? Which cells divide? You mean it replicates with the lysogenic cycle? I thought that was only applicable to bacteria, as human cells don't clone each other--at least NK, B, and T cells, don't "divide". They come from stem cells in the bone marrow.

Just wanted to thank everyone who has responded so far - I only posted the question a short while ago and there has been some very interesting discussion already. Thanks, everybody! I'm looking forward to more...

Regarding how XMRV replicates, I got that from Judy Mikovitz, here is a quote from a presentation she made:

Now let's talk about how you detect retroviruses, because that's important in thinking about how we found this virus and how we study it in the laboratory. So the viral life-cycle as I just described; once you have the DNA integrated into the chromosome, once it's integrated to the reverse transcriptase integrated it into the chromosome. It's there and it replicates every time your cell divides and your DNA replicates. So if your cell isn't dividing, theoretically it's just latent. It's just there in the DNA and it's not making more viruses, it's not making copies of itself. It's not infecting more cells. This is a good state if you have a retrovirus is to just shut down the transcription.

I agree, this does not entirely make sense as immune cells do not 'divide', except when they are differentiated from new WBCs, anyway that is how I understand things, maybe a biologist here can clarify what she means. So I assume that therefore the XMRV must be infecting the stem cells somewhere in the process where they differentiate into WBCs. But I believe she is just speculating there, I have not read any reports of studies proving a replication mechanism. Also she appears to be hopeful that due to the slow replication cycle, blocking the transcription process should easily defeat viral replication.

Does XMRV hijack cells and prevent programmed cell death (apoptosis)? If so, I know there are natural supplements that can turn apoptosis back on (not sure I'm saying this the right way). Just thinking that if ART can be used to deal with XMRV when the cell is replicating and other treatment to cause the infected cells that are not replicating to die. And then Peptide T to block any XMRV that "got away" from infecting other cells?

I'm too foggy to follow much science lately, so I hope this makes sense but don't blast me if it doesn't! :Retro smile:

I don't have much of a guess here except to say we need more studies. I read recently from the initial developers of AZT that when they first came out with it, many people doubted that it would work since AZT only inhibited replication and not HIV integration into DNA. But, as we know, it did end up working well enough to buy people time to the next antiretroviral. So, I would say just because XMRV replicated slowly, there should be no assumptions made that this means it doesn't have a huge impact on the immune system.

Also, B-cells definitely divide IIRC. And I suspect T-cells do too. From my notes, Dr. Klimas talked about how having mono (which makes B-cells with ?XMRV in them divide enourmously) might be why people get sick with CFS after. Whereas before, they might have had less copies.

Third, my impression has been that viral replication can be independent of cell division. (not just for XMRV but other viruses also)

Kurt, interesting points. I believe XMRV infects, then sits there unless turned on. Then it replicates, infecting more cells. But then, the conditions can make it go dormant. Then, something can turn it one again. At some point, it starts causing problems in immune system able to fight latent viruses. Then the inflammation, then in time, a loop is developed. But, I believe some people, if they can stop the replication of the virus or keep it down, may be able to crawl out of that loop and find some symptom relief. But for some, they may need some help with immune system, treatment of latent viruses, immune system modulators, boost for endocrine system, all the stuff we see so many including in treatment now, along with stopping or greatly hindering XMRV replication.

I have wondered about this, too. If XMRV is the culprit, two things seem to offer some hope for a limited treatment period, followed by a drug-free remission: 1) some people with CFS get better and 2) about 9 out of 10 people that are XMRV positive are not sick according to Lombardi et al. Of course both of these could be due to extra genetic susceptibility on the part of those who are really sick, and achieving escape velocity may not be possible for such people.

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So 9 out of 10 people who test xmrv positive aren't even sick?? I want to get tested, but I don't want to spend the money if the test isn't showing positives to people who are really sick. I'm really sick, maybe I should wait and see a little longer on how this all pans out.

Kurt, interesting points. I believe XMRV infects, then sits there unless turned on. Then it replicates, infecting more cells. But then, the conditions can make it go dormant. Then, something can turn it one again. At some point, it starts causing problems in immune system able to fight latent viruses. Then the inflammation, then in time, a loop is developed. But, I believe some people, if they can stop the replication of the virus or keep it down, may be able to crawl out of that loop and find some symptom relief. But for some, they may need some help with immune system, treatment of latent viruses, immune system modulators, boost for endocrine system, all the stuff we see so many including in treatment now, along with stopping or greatly hindering XMRV replication.
Tina

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I know people are saying that XMRV must cause the NK cell dysfunction and T and B cell problems, but that actually makes no sense if you read the prostate cancer studies. There the XMRV is believed to disrupt communication between neuroendocrine cells, the prostate is in the neuroendocrine system and has that type of tissue. And since the WPI hypothesis is that this is a nearly identical gene sequence (I believe there were only 6-8 SNP variations between CFS XMRV and other XMRVs), one would expect that in CFS the virus does the same thing. It likely prefers specific tissues, can only attach in certain places and do certain things. And if it has altered neuroendocrine functions that would persist until cell replication, so we would need to use a mild antiretroviral that we could tolerate and then also treat the HPA type problems that we already know are neuroendocrine.

personally, because i am so sick, if i test positive for the virus, i am going to begin AZT and Isentress. its definitely better to take 2 drugs than 1.
The problem is affording Isentress. even HIV positive people have to get special forms filled out to get the meds.

i am wondering whether i could somehow pay for 6 months of the drugs and if i improve, i can apply for special priviledge to get them...but it probably still won't work unless there are more studies showing that CFS people have the virus...doesn't look like that's going to happen anytime soon. i expect the swedish study to be more of the same.

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Mikovitz and many others have specifically stated NOT to use AZT. Why do you want to use that toxic drug? I think there will be much better options if/when the WPI finding is validated and researchers turn to the next problem. AZT can cause mitochondrial problems, and that really would be a bad idea for CFS. They will find some other way to block XMRV activity, they are working on Peptide T.

So 9 out of 10 people who test xmrv positive aren't even sick?? I want to get tested, but I don't want to spend the money if the test isn't showing positives to people who are really sick. I'm really sick, maybe I should wait and see a little longer on how this all pans out.

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That is a good point, if so many healthy people have XMRV we really should have a validated causal model before worrying too much about whether we are positive. There should be a demonstrated mechanism of pathogenic activity. Meaning experimental evidence of how the virus causes illness and not just theory, which is all we have right now.

Not quite. If we were to assume that all cases of CFS are caused by XMRV, and assume that XMRV is present in the general population at a rate of about 4%, and that CFS is present in the general population of about 0.4%, then you could say that 9 out of 10 people who have been infected with XMRV are currently not sick with CFS.

I have not seen anyone yet treated for xmrv? Or is this something I missed. Sunny Gal how long have you been taking it?
Are there side effects? What is it suppose to do?

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The betulinic acid I'm on comes from a company in Italy that makes plant stem cells (just shoots and buds of plants, nothing like human stem cells). It's apparently been used for HIV and cancer tumors. It's supposed to work by inducing apoptosis, or programmed cell death. I guess the idea is that infected cells have turned off apotosis and by turning it back on you are able to take out the infection by allowing the cell to finally die.

I've been taking it since early January so it's too early to know how it works. My doc who put me on it is an ND and said it busts up tumors in about 6 months so I'm guessing it will take 6 or so months of being on it for it to address XMRV, if it actually will. Of course this is all new so no one knows how it will actually work out.

Plant stem cells are generally very mild and don't cause much in the way of reactions. I did feel a bit flu-like and had a mild (99.4ish) fever for the first day or two I was on it.

sunnygal...would your doctor prescribe antiretrovirals if you asked him? just curious if he offered them or not...

i always think that unless i take actual approved drugs, the substance will not absorb to a degree that can help me. i have read that betulinic acid derivatives have acitivity against HIV-2 but i wonder if the acid alone would absorb properly...

do you know if any other patients of your doctor are taking it and how they are doing on it?

thanks
sue

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Hi Sue,

I'm sorry... I posted a reply right after your post, but I just noticed my post didn't show up for some reason. I don't know what happened. Sorry for not noticing sooner!

I don't know if my doc (a Lyme MD) would prescribe antiretrovirals if I asked him for them. I haven't seen him since I got my + XMRV test results (his assistant gave me the results and she refused to even speculate on XMRV). The last time I saw my doc was when he gave me the lab order for XMRV testing at the end of November and he didn't mention potential treatments at that time, other than the betulinic acid that the Lyme ND he has me seeing already planned to start me on.

I suspect that he's not the type to go with the current antiretrovirals, at least not for me. He knows I'm very toxic and highly reactive to everything, so I doubt he'd want to go with antiretrovirals for me since they're so toxic. I have an appointment with him this week, though, and I can post back here if he suggests any possible treatments for my XMRV. I plan to ask him about Peptide T since it's supposedly not toxic at all.

I'm not sure what you mean regarding your concern for substances absorbing properly? The betulinic acid I take is a liquid which of course absorbs very readily. Do you perhaps mean you're not sure the natural substances would be as potent as a pharmaceutical?

I personally try to avoid pharmaceuticals as they are un-natural to the body and usually toxic to some degree. My body doesn't do very well with them even though they are so potent (or perhaps because they are so un-naturally potent). The plant stem cells such as betulinic acid tend to cause few adverse reactions and since they are plant based they usually have multiple actions (unlike pharma drugs). For example, betulinic acid is anti-viral (including retroviruses, I guess), anti-bacteria, anti-fungal and anti-parasitic. The betulinic acid is supposed to bust up tumors in about 6 months, so while it takes longer to work that pharma drugs do, it works better with the body without toxicity issues.

I started on betulinic acid in early December and I did have a day or two of feeling a bit feverish and yucky when I first started on it but after that had no obvious adverse reactions. I worked up to the full dose slowly (a caution I take with all new supplements/meds because I tend to react to everything) and was only on the full dose for a couple of weeks when my blood work came back showing that my white blood cell count had crashed. So, my doc had me cut back on all of my bug killers by half (including the betulinic acid) for the past couple of weeks. This coming week my doc will modify my protocol to take into account my blood work. I believe the idea is that my white blood cell count crashed due to infected WBCs being killed off by my treatment.

As I was only on the full dose of betulinic for a few weeks it's too early to know if it's helping to address XMRV. I can report back here my progress over the next several months if anyone is interested. I do know another patient of my doctor's who is also using the betulinic acid. He started on it after I did, though, so it's too early to know how it's helping him, too.

As I was only on the full dose of betulinic for a few weeks it's too early to know if it's helping to address XMRV. I can report back here my progress over the next several months if anyone is interested. I do know another patient of my doctor's who is also using the betulinic acid. He started on it after I did, though, so it's too early to know how it's helping him, too.

Sunny

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I think pretty much everyone would like to know how you get on, I would.